Bioequivalence of tenofovirdisoproxil fumarate tablets in Chinese healthy volunteers

LOU Jin-feng; SUN Ji-xuan; ZHOU Ling; DING Yan-hua; LIU Shuang; HUO Dan-dan; ZHANG Ying-qi; LIANG Wen-zhong

Abstract：Objective:To investigate the bioequivalence of 2 formulations of tenofovirdisoproxil fumarate tablets in Chinese healthy volunteers under fasting and postprandial conditions.Methods:In a randomized two-way crossover study,26 healthy male volunteers were divided into two groups and were administered with a single oral dose of test or reference formulations containing 300 mg tenofovirdisoproxil fumarate under fasting and postprandial conditions.The blood samples were collected at predetermined time intervals up to 72 h.The plasma concentration of tenofovir was determined by LC-MS/MS.The pharmacokinetic parameters were estimated by WinNonlin software.Results:The established LC-MS/MS method had linear calibration range over 1.00 ～600 ng·mL-1 with a limit of quantitation (LLOQ) of 1.00 ng· mL-1 for tenofovir in human plasma.The intra-and inter-batch standard deviations were less than 15％.The pharmacokinetic parameters for the test and reference tablets under fasting conditions were as follows:Tmax(0.5 ±2) and (0.5 ± 1.5) h,Cmax(291.83 ±66.29) and (321.22 ±74.65) ng·mL-1,t1/2(19.98 ±2.27) and (21.00 ±2.93) h,AUC0-72h(2404.73 ±532.72) and (2522.65 ±567.08) h·ng·mL-1 The pharmacokinetic parameters for the test and reference tablets under postprandial conditions were as follows:Tmax(0.75 ±5) and (1 ±8) h,Cmax(261.31 ±101.27) and (292.22 ±122.67) ng·mL-1,t1/2 (19.38 ±2.39) and (19.44 ±2.26) h,AUC0-72h(3 043.16 ±731.12) and (3 147.96 ±930.67) h·ng·mL-1,respectively.Conclusion:The method is suitable for the pharmacokinetic study of tenofovirdisoproxil fumarate tablets,and the two preparations are bioequivalent.